Strain analysis reveals subtle systolic dysfunction in confirmed and suspected myocarditis with normal LVEF. A cardiac magnetic resonance study.

AIMS: Lake Louise Criteria (LLC) are time-dependent and some acute myocarditis (AM) with preserved left ventricular ejection fraction (LVEF) could be missed, due to the limited accessibility of Cardiac Magnetic Resonance (CMR). We aimed to assess the potential value of cardiac strain measured by feature tracking (FT) imaging in this population. METHODS AND RESULTS: Eighty-three patients with clinically suspected AM and normal LVEF were divided into 39 "confirmed AM" (positive LLC) and 44 "suspected AM" (negative LLC). An age and gender-matched sample of 42 normal subjects underwent CMR. In all groups, FT-derived biventricular strains and STE- global longitudinal strain (GLS) were assessed, being regularly measurable. Strain values < 5th percentile of the control group were considered abnormal. "Suspected" and "confirmed" AM were similar, except for medium time of CMR evaluation (5.2 vs 1 months from presentation, respectively; p = 0.004). Compared to healthy controls, both "suspected" and "confirmed" AM showed significantly impaired strain values. LV-global circumferential strain (GCS), right ventricular GCS and LV-GLS were abnormal in 15.4% and 15.9%, 20.5% and 15.9%, 7.7% and 9.1% in "confirmed" and "suspected" AM, respectively. STE analysis confirmed the results on LV-GLS, however a weak correlation emerged between STE and CMR-FT LV-GLS (p = 0.08). CONCLUSIONS: Compared to STE, CMR-FT analysis provided a more comprehensive and complementary biventricular strain evaluation that resulted similar in "confirmed" and "suspected" AM with normal LVEF. Conversely, mostly biventricular GCS was significantly reduced in up to 20% of patients, compared to healthy controls.

Non-alcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in essential hypertension.

BACKGROUND AND AIM: Insulin resistance is recognized as the pathophysiological hallmark of non-alcoholic fatty liver disease (NAFLD). A relation between insulin sensitivity and left ventricular morphology and function has been reported in essential hypertension, where a high prevalence of NAFLD has been recently found. We investigated the inter-relationship between left ventricular morphology/function, metabolic parameters and NAFLD in 86 never-treated essential hypertensive patients subdivided in two subgroups according to the presence (n = 48) or absence (n = 38) of NAFLD at ultrasonography. METHODS AND RESULTS: The two groups were similar as to sex, age and blood pressure levels. No patient had diabetes mellitus, obesity, hyperlipidemia, or other risk factors for liver disease. Body mass index, waist circumference, triglycerides, glucose, insulin, homeostasis model of assessment index for insulin resistance (HOMA-IR), aspartate aminotransferase and alanine aminotransferase were higher and adiponectin levels were lower in patients with NAFLD than in patients without NAFLD, and were associated with NAFLD at univariate analysis. Patients with NAFLD had similar prevalence of left ventricular hypertrophy compared to patients without NAFLD, but a higher prevalence of diastolic dysfunction (62.5 vs 21.1%, P < 0.001), as defined by E/A ratio <1 and E-wave deceleration time >220 ms. Diastolic dysfunction (P = 0.040) and HOMA-IR (P = 0.012) remained independently associated with NAFLD at backward multivariate analysis. CONCLUSIONS: Non-alcoholic fatty liver disease was associated with insulin resistance and abnormalities of left ventricular diastolic function in a cohort of patients with essential hypertension, suggesting a concomitant increase of metabolic and cardiac risk in this condition.

Current perspective new insights into the molecular basis of familial dilated cardiomyopathy.

Genetic disease transmission has been identified in a significant proportion of patients with dilated cardiomyopathy (DCM). Variable clinical characteristics and patterns of inheritance, as well as recent molecular genetic data, indicate the existence of several genes causing the disease. Several distinct subtypes of familial DCM have been identified. Autosomal dominant DCM is the most frequent form (56% of our cases), and several candidate disease loci have been identified by linkage analysis. Three disease genes are presently known: the cardiac actin gene, the desmin gene, and the lamin A/C gene. This latter gene has recently been found to be responsible for both the autosomal dominant form of DCM with subclinical skeletal muscle disease (7.7% of cases) and the familial form with conduction defects (2.6% of cases) or the autosomal dominant variant of Emery-Dreifuss muscular dystrophy. The autosomal recessive form of DCM accounts for 16% of cases and is characterized by a worse prognosis. An X-linked form of DCM (10% of cases) manifests in the adult population and is due to mutations in the dystrophin gene. In the rare infantile form of DCM, mutations in the G4.5 gene have been identified. Finally, some of the rare unclassifiable forms (7.7% of cases) may be due to mitochondrial DNA mutations. Clinical and experimental evidence based on animal models suggest that, in a large number of cases, DCMs are diseases of the cytoskeleton. However, other causes, such as alterations in regulatory elements and in signaling molecules, are possible. Moreover, other genes called modifier genes can influence the severity, penetrance, and expression of the disease, and they will be a main objective of future investigations. Familial DCM is frequent, cannot be predicted on a clinical or morphological basis and requires family screening for identification. The advances in the genetics of familial DCM can allow improved diagnosis, prevention and genetic counseling, and represent the basis for the development of new therapies.

[Echocardiographic follow-up of patients with heart failure. Which parameters should be measured? How often?]. / Il follow-up ecocardiografico del paziente con scompenso cardiaco. Quali parametri misurare? Con quale frequenza?

The echocardiographic evaluation keeps a relevant place in the evaluation of patients with heart failure and left ventricular systolic dysfunction, not only for its contribution to the diagnosis, prognostic stratification and comprehension of pathogenetic mechanisms, but also for the analysis of the evolution of the disease and the response to optimal medical therapy. On the other hand, the role of echocardiography in the follow-up of patients with diastolic dysfunction is still unclear. In patients with heart failure and left ventricular systolic dysfunction the analysis of changes in left ventricular function and dimension during follow-up is particularly relevant to recognize the potential benefit of optimal medical therapy with ACE-inhibitors and beta-blockers and their prognostic significance. The echo-Doppler hemodynamic evaluation is also of clinical and prognostic value particularly for the recognition of the persistence or (re)appearance of restrictive filling pattern during follow-up. Moreover, in patients with persistent severe left ventricular systolic dysfunction, the evaluation of right ventricular function may allow for the identification of a subset of patients at high risk for cardiovascular events. A practical flow-chart of echocardiographic assessment of patients with heart failure and left ventricular systolic dysfunction includes the following steps: 1) after 3 to 6 months on optimal therapy, to detect the persistence of restrictive filling pattern, if present at diagnosis; 2) after 12 to 24 months, to analyze the response of left ventricular function and dimension to optimal medical treatment; 3) serial examinations, according to the stage of the disease or to the episodes of worsening heart failure, to identify echocardiographic indicators of disease progression, such as worsening of left ventricular and/or right ventricular function or (re)appearance of restrictive filling pattern. The changes in these parameters seem to have a relevant prognostic significance to define the risk profile of patients with heart failure and left ventricular systolic dysfunction.

[Contribution of echocardiography to the diagnosis of patients with chronic heart failure]. / Contributo dell'ecocardiografia alla diagnosi eziologica nel paziente con scompenso cardiaco cronico.

The echocardiographic examination is generally performed in patients with heart failure and it often gives a significant contribution to the differential diagnosis. Firstly, the evaluation of left ventricular pump function by measuring the ejection fraction (EF) can distinguish patients with heart failure into two different groups, with depressed or preserved EF. The most frequent causes of heart failure and depressed EF are coronary artery disease, idiopathic dilated cardiomyopathy (DCM) and hypertensive heart disease. Although the echocardiographic features of coronary artery disease versus idiopathic DCM may be similar, the demonstration of inducible ischemia at dobutamine echocardiographic test suggests the presence of significant coronary artery disease and may be useful in the selection of cases for coronary arteriography. The association of left ventricular hypertrophy, hypokinesis and, sometimes, significant dilation is compatible with hypertensive heart disease or end-stage hypertrophic cardiomyopathy. No useful echocardiographic findings can identify the patients with genetic DCM or affected by myocarditis from other cases with idiopathic DCM. Some advanced cases of right ventricular dysplasia/cardiomyopathy may show a biventricular involvement and mimic DCM; these patients are usually characterized at echo by predominant right ventricular dilation and multiple a-dyskinetic bulges in the absence of pulmonary hypertension. Very difficult to manage are the patients with significant left ventricular dysfunction and severe valvular heart disease (such as aortic stenosis or mitral regurgitation). According to the literature, the left ventricular systolic function is relatively preserved (EF > 40%) in 30-40% of patients with heart failure. In these cases a diastolic dysfunction may be hypothesized. Echo-Doppler evaluation can be helpful in the recognition of signs of increased left ventricular stiffness ("restrictive filling pattern") and of increased filling pressures. In the differential diagnosis one must first consider the most frequent heart disorders that may present with this clinical syndrome, coronary artery disease and hypertensive heart disease. Furthermore, other less common diseases characterized by heart failure due to predominant diastolic dysfunction are the following: hypertrophic and restrictive cardiomyopathies, infiltrative heart diseases, such as amyloidosis, and constrictive pericarditis. Restrictive cardiomyopathy is characterized by heart failure and preserved left ventricular EF in the absence of significant ventricular dilation and hypertrophy; typical, although not pathognomonic, echocardiographic features are atrial enlargement ad restrictive filling pattern. In distinguishing constrictive pericarditis from restrictive cardiomyopathy useful Doppler signs are the wide respiratory variability in flow velocities at mitral and tricuspid levels, due to increased ventricular interdependence caused by the presence of an abnormally rigid pericardium.

[Heart failure due to diastolic dysfunction: the treatment principles]. / Scompenso cardiaco da disfunzione diastolica: principi di trattamento.

The clinical relevance of diastolic dysfunction in heart failure has recently been emphasized. In fact, the presence of signs of heart failure does not imply a depressed left ventricular systolic function; moreover, the severity of heart failure and effort tolerance are more closely related to diastolic than to systolic indexes. However, the principal trials about the treatment of heart failure were mainly addressed to patients with significant left ventricular systolic dysfunction, whereas the optimal therapy for diastolic dysfunction is not well known. The aim of this review was to assess the rationale and the therapeutic options in heart failure due to diastolic dysfunction. A diastolic dysfunction can be exclusive or associated with systolic dysfunction, as in dilated cardiomyopathy. It has to be noted that in this disease an improvement of diastolic function was demonstrated for most of the drugs currently employed in the treatment of heart failure, such as vasodilators, ACE inhibitors, beta-blockers, digitalis, and other inotropic drugs. Moreover, the favorable effect of the treatment on diastolic parameters (reduction of left ventricular filling pressure, regression of restrictive filling pattern) is associated with a positive prognostic impact. The main objective of the treatment of heart failure with preserved left ventricular systolic function is to control the symptoms by means of lowering high left ventricular filling pressure without significantly lowering cardiac output. According to the therapeutic guidelines of the American College of Cardiology/American Heart Association Task Force, the drugs indicated to treat symptomatic patients with heart failure and preserved left ventricular systolic function are diuretics and nitrates. Potentially useful, but with insufficiently proven efficacy are beta-blockers, calcium antagonists and ACE inhibitors, whereas direct vasodilators and inotropic drugs were considered inadvisable. It is important to remember that the treatment might possibly be oriented to the cause and also to the possible precipitating factors of the heart failure syndrome (i.e. ischemia, tachycardia, arrhythmias, hypertension). In conclusion, considering the relatively common incidence of heart failure due to prevalent diastolic dysfunction, and the few available data about the therapeutic options in these patients, large multicenter trials devoted to the treatment of this syndrome are needed.

Familial dilated cardiomyopathy: evidence for genetic and phenotypic heterogeneity. Heart Muscle Disease Study Group.

OBJECTIVES: This study was performed to evaluate the characteristics, mode of inheritance and etiology of familial dilated cardiomyopathy (FDC). BACKGROUND: A genetic form of disease transmission has been identified in a relevant proportion of patients with dilated cardiomyopathy (DCM). Variable clinical characteristics and patterns of inheritance, and an increased frequency of cardiac antibodies have been reported. An analysis of FDC may improve the understanding of the disease and the management of patients. METHODS: Of 350 consecutive patients with idiopathic DCM, 281 relatives from 60 families were examined. Family studies included clinical examination, electrocardiography, echocardiography and blood sampling. Of the 60 DCM index patients examined, 39 were attributable to FDC and 21 were due to sporadic DCM. Clinical features, histology, mode of inheritance and autoimmune serology were examined, molecular genetic studies were undertaken and the difference between familial and sporadic forms was analyzed. RESULTS: Only a younger age (p = 0.0005) and a higher ejection fraction (p = 0.03) could clinically distinguish FDC patients from those with sporadic DCM. However, a number of distinct subtypes of FDC were identified: 1) autosomal dominant, the most frequent form (56%); 2) autosomal recessive (16%), characterized by worse prognosis; 3) X-linked FDC (10%), with different mutations of the dystrophin gene; 4) a novel form of autosomal dominant DCM with subclinical skeletal muscle disease (7.7%); 5) FDC with conduction defects (2.6%), and 6) rare unclassifiable forms (7.7%). The forms with skeletal muscle involvement were characterized by a restrictive filling pattern; the forms with isolated cardiomyopathy had an increased frequency of organ-specific cardiac autoantibodies. Histologic signs of myocarditis were frequent and nonspecific. CONCLUSIONS: Familial dilated cardiomyopathy is frequent, cannot be predicted on a clinical or morphologic basis and requires family screening for identification. The phenotypic heterogeneity, different patterns of transmission, different frequencies of cardiac autoantibodies and the initial molecular genetic data indicate that multiple genes and pathogenetic mechanisms can lead to FDC.

Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol. The Heart-Muscle Disease Study Group.

OBJECTIVES: The purpose of this study was to analyze whether long-term treatment with the nonselective beta-adrenergic blocking agent carvedilol may have beneficial effects in patients with dilated cardiomyopathy (DCM), who are poor responders in terms of left ventricular (LV) function and exercise tolerance to chronic treatment with the selective beta-blocker metoprolol. BACKGROUND: Although metoprolol has been proven to be beneficial in the majority of patients with heart failure, a subset of the remaining patients shows long-term survival without satisfactory clinical improvement. METHODS: Thirty consecutive DCM patients with persistent LV dysfunction (ejection fraction < or =40%) and reduced exercise tolerance (peak oxygen consumption <25 ml/kg/min) despite chronic (>1 year) tailored treatment with metoprolol and angiotensin-converting enzyme inhibitors were enrolled in a 12-month, open-label, parallel trial and were randomized either to continue on metoprolol (n = 16, mean dosage 142+/-44 mg/day) or to cross over to maximum tolerated dosage of carvedilol (n = 14, mean dosage 74+/-23 mg/day). RESULTS: At 12 months, patients on carvedilol, compared with those continuing on metoprolol, showed a decrease in LV dimensions (end-diastolic volume -8+/-7 vs. +7+/-6 ml/m2, p = 0.053; end-systolic volume -7+/-5 vs. +6+/-4 ml/m2, p = 0.047), an improvement in LV ejection fraction (+7+/-3% vs. -1+/-2%, p = 0.045), a reduction in ventricular ectopic beats (-12+/-9 vs. +62+/-50 n/h, p = 0.05) and couplets (-0.5+/-0.4 vs. +1.5+/-0.6 n/h, p = 0.048), no significant benefit on symptoms and quality of life and a negative effect on peak oxygen consumption (-0.6+/-0.6 vs. +1.3+/-0.5 ml/kg/min, p = 0.03). CONCLUSIONS: In DCM patients who were poor responders to chronic metoprolol, carvedilol treatment was associated with favorable effects on LV systolic function and remodeling as well as on ventricular arrhythmias, whereas it had a negative effect on peak oxygen consumption.

Cardiac tamponade: an unusual, fatal complication of infective endocarditis.

Infective endocarditis still occurs in Western countries and so far, it has been an important medical problem. The spectrum of infective endocarditis complications may be extremely wide. We report two unusual cases of infective endocarditis complicated with heart rupture and pericardial effusion. In one case, the infective process spread from the aortic valve developing a sinus of Valsalva aneurysm with subsequent aortic perforation. The perforation reached the right auricular epicardial region with subsequent epicardial rupture and hemopericardium. In the other patient, an infective process of the aortic cusps induced the formation of multiple abscesses in the left ventricle and in the right atrium. An annular abscess of the tricuspid valve was found. From the right atrium, an infected fistula spread through the atrial wall and perforated the epicardial surface of the right auricle. Aside from the rare occurrence of these complications in patients affected with infective endocarditis, these cases are of clinical interest because they raise the problem of the need of greater sensitivity to the diagnosis of endocarditis and proper diagnostic approach.

[Clinical polymorphic presentation and natural history of active myocarditis: experience in 60 cases]. / Polimorfismo clinico di presentazione e storia naturale della miocardite attiva: esperienza su 60 casi.

Eight-hundred thirty patients (pts) with suspected myocardial disease of undefined etiology were observed from 1978 to 1996. In 350 pts, the clinical diagnosis was of dilated cardiomyopathy (DCM) or myocarditis. An endomyocardial biopsy was performed on all patients and in 54 of them (15%), an active myocarditis was identified. In six cases, myocarditis was detected at autopsy. There were 37 male patients and 23 females, with an average age of 35.5 +/- 15 years (range 1.67). Mean time interval between clinical onset and diagnosis was 4 +/- 10 months. Clinical presentation was characterized in 4 cases by fulminant myocarditis (Group I), in 8 cases by chest pain (Group II), in 14 cases by arrhythmia (Group III: hypokinetic in 9 pts and hyperkinetic in 5) and, in the last 34 pts, by congestive heart failure (CHF) (Group IV). Improvement was defined at 9 +/- 3 months according to a clinical score based on left ventricular shortening fraction (increase > or = 5 units), New York Heart Association Class improvement by (at least one Class) and left ventricular end-diastolic diameter (decrease > or = 10%). The main clinical and instrumental parameters characterizing the groups were: a more severe dilatation and left ventricular dysfunction in the pts belonging to Group I or IV with respect to those in Group II and III; a significantly worse prognosis in terms of evolution in DCM or death/cardiac transplantation (CT) in the pts from the Group II and III. After a follow-up period of 48 +/- 46 months, the mortality in the four groups was: 100% (4/4), 0% (0/8), 21% (3/14), 38% (13/34). Fifty percent of deaths were concentrated in the first 2 years of follow-up. Left ventricular end-diastolic diameter (OR 1.09, p < 0.05), age (OR 0.95), presence of left ventricular bundle branch block (OR 2.32), right ventricular function (OR 2.43) at clinical onset and the status of improvement at 9 +/- 3 months of follow-up (OR 0.24, p < 0.05) are predictors of evolution in DCM or death/CT for the pts with onset from CHF (Group IV). Immunosuppressive treatment has been utilized for the 76% of the pts. No conclusion can be drawn on the efficacy of this therapy, but no adverse events significantly related to therapy have been observed in a 9 +/- 3 months follow-up period. In conclusion, myocarditis can show a clinical presentation polymorphism, which influences the prognosis and natural history of the disease. Evolution in DCM and adverse events (death/CT) are more common in Groups I and IV. Some simple parameters evaluated at clinical presentation and the proposed classification as "improved" or "not improved" after a short-term follow-up (9 +/- 3 months) show good predictive accuracy. The present study does not allow us to draw any conclusion about the efficacy of immunosuppressive treatment. A randomized, controlled, large-scale trial, with adequate follow-up and advanced histological diagnosis techniques will help define the role of immunosuppressive therapy and patient eligibility criteria for this treatment.

Persistence of restrictive left ventricular filling pattern in dilated cardiomyopathy: an ominous prognostic sign.

OBJECTIVES: We sought to assess the prognostic implications of the evolution of restrictive left ventricular filling pattern (RFP) in dilated cardiomyopathy (DCM). BACKGROUND: Previous work has demonstrated that a RFP in DCM is associated with a poor prognosis. Few data are available on the prognostic implications of the evolution of this pattern. METHODS: The evolution of left ventricular filling was studied by Doppler echocardiography in 110 patients with DCM. According to the left ventricular filling pattern at presentation and after 3 months of treatment, the patients were classified into three groups: Group 1A (n = 24) had persistent restrictive filling; Group 1B (n = 29) had reversible restrictive filling; and Group 2 (n = 57) had nonrestrictive filling. RESULTS: During follow-up (41 +/- 20 months), mortality plus heart transplantations was significantly higher in Group 1A than in Groups 1B and 2 (p < 0.0001). On multivariate analysis, the model incorporating E wave deceleration time at 3 months was more powerful at predicting mortality with respect to this variable at baseline (p = 0.0039). Clinical improvement at 1 and 2 years was significantly more frequent in Groups 1B and 2 than in Group 1A (p < 0.0001 at 2 years). CONCLUSIONS: In patients with DCM, the persistence of restrictive filling at 3 months is associated with a high mortality and transplantation rate. The patients with reversible restrictive filling have a high probability of improvement and excellent survival. Doppler echocardiographic reevaluation of these patients after 3 months of therapy gives additional prognostic information with respect to the initial study.

Familial right ventricular dysplasia with biventricular involvement and inflammatory infiltration. Heart Muscle Disease Study Group.

The aetiology of right ventricular dysplasia/cardiomyopathy is presently unknown. A genetic background has been suggested, but myocarditis may play a part in its pathogenesis. Two familial cases of right ventricular dysplasia, one of whom had also a diagnosis of myocarditis, are reported. Both patients presented with ventricular arrhythmias. The father subsequently had a "flu-like" syndrome, heart failure, and biventricular dysfunction; "active" myocarditis was found at endomyocardial biopsy. Then the patient died suddenly. The daughter developed progressive biventricular dysfunction; then she was resuscitated from a cardiac arrest, and subsequently died suddenly. In both patients necropsy showed severe right ventricular atrophy and fibro-adipose substitution, associated with biventricular fibrosis. Inflammatory infiltration was also present in the first patient. This study shows the association of right ventricular dysplasia and myocarditis in the same family. These cases may represent a link between inherited and acquired ("inflammatory") forms of the disease.

Genetic factors in dilated cardiomyopathy.

Recent studies have demonstrated that genetic factors are likely to play a major role in the pathogenesis of idiopathic dilated cardiomyopathy (IDC). In clinical surveys, a familial trait has been demonstrated in 20 to 30% of idiopathic dilated cardiomyopathy patients (familial dilated cardiomyopathy). Molecular genetic studies have confirmed the clinical hypothesis of genetic heterogeneity in familial dilated cardiomyopathy, and are currently producing relevant advances in the understanding of this disease. The autosomal dominant form is considered to be the most frequent form of inherited idiopathic dilated cardiomyopathy. After the exclusion of a large series of candidate genes, the first familial dilated cardiomyopathy gene has been mapped to the long arm of chromosome 9. A second locus has been found on chromosome 1. Moreover, in two large families, characterized by a peculiar form of conduction delays and later development of myocardial dysfunction, the disease loci have been mapped to chromosome 1 and 3, respectively. The identification of the disease genes is in progress. In families with X-linked dilated cardiomyopathy, the disease gene has been identified as the dystrophin gene. The 5' end of the gene appears to be the critical region for the development of dilated cardiomyopathy without clinical evidence of muscle dystrophy. Furthermore, other cytoskeletal proteins, such as adhalin, could be involved in the pathogenesis of familial dilated cardiomyopathy. In familial right ventricular cardiomyopathy (or arrhythmogenic right ventricular dysplasia) characterized by isolated or prevalent right ventricular involvement, three different disease loci have been identified so far: two localized on the long arm of chromosome 14 and one on chromosome 1. The disease genes are still unknown and are currently under investigation. The study of the genetic factors at the molecular level is starting to elucidate the pathogenetic mechanisms of idiopathic dilated cardiomyopathy. These findings will also have relevant clinical and therapeutic implications.

Metoprolol in dilated cardiomyopathy: is it possible to identify factors predictive of improvement? The Heart Muscle Disease Study Group.

BACKGROUND: Some controlled clinical trials showed a beneficial effect of beta-blockers on symptoms, exercise tolerance, and left ventricular function in dilated cardiomyopathy. The purpose of this study was to investigate if there are clinical variables at baseline that could predict a favorable response to long-term metoprolol therapy. METHODS AND RESULTS: Since November 1987, 94 consecutive patients with dilated cardiomyopathy and left ventricular ejection fraction less than 0.40 were treated with metoprolol (mean final dosage, 136 +/- 32 mg) associated with tailored medical therapy with digitalis, diuretics, and angiotensin-converting enzyme inhibitors. Eighty-four surviving patients had a complete 2-year noninvasive follow-up period. Ten patients died or were transplanted before the final assessment. Improvement was defined according to a clinical score based on left ventricular ejection fraction (increase > or = 10 U), left ventricular end-diastolic diameter (decrease > or = 10%), regression of restrictive filling pattern, New York Heart Association functional class, exercise tolerance (increase > or = 2 minutes), and cardiothoracic ratio (decrease > or = 10%). According to these criteria, 48 patients (51.1%) were classified as improved. Multivariate analysis identified a group of patients with a history of mild hypertension (blood pressure between 140/90 and 170/100 mmHg) and significantly higher probability of improvement with longterm metoprolol (odds ratio [OR], 2.22; 95% confidence interval, 1.25-3.94; P = .007). Among the 71 patients with normal blood pressure (< 140/90 mmHg), heart rate in upright position (100 vs 75 beats/min: OR, 2; 95% confidence interval, 1.38-4.94; P = .003), left ventricular ejection fraction 0.20-0.33 versus less than 0.20 (OR, 4.72; 95% confidence interval, 1.06-21.04; P = .042), and New York Heart Association class I-II versus III-IV (OR, 2.74; 95% confidence interval, 0.97-7.75; P = .05) were significantly associated with a positive response to metoprolol. At baseline, both supine and upright heart rate were significantly higher in patients who improved, but heart rate in the upright position was the most significant predictor of improvement in patients with normal blood pressure at multivariate analysis. CONCLUSIONS: According to the authors' logit model, patients with a history of mild hypertension or with a higher resting heart rate, associated with controlled symptoms of heart failure (New York Heart Association class I-II) or moderate to severe left ventricular ejection fraction (range, 0.20-0.33) showed a remarkable probability of long-term (2-year) improvement on metoprolol.